The muscarinic acetylcholne receptor in adult heart is located mainly in the atria and is innervated by the vagus nerve. Vagal interactions with the heart have been implicated in cardiac arrythmias and some types of heart disease. Little is known about the protein molecule since all solubilization procedures tried to date have apparently destroyed ligand binding activity. To overcome this difficulty, the synthesis of active site directed alkylating agents for the muscarinic acetylcholine receptor is proposed. These labels will permit investigation of the topology of the receptor ligand binding sites as well as sites for antiarrythmia drugs. Since the labels will remain covalently bound to the receptor following solubilization they will serve as useful markers during purification of the protein. Thermodynamic and kinetic studies of ligand binding to the membrane-bound receptor are also proposed. These data permit determination of thermodynamic dissociation constants and detection of ligand-induced conformational changes in the minute time domain. These experiments will complement studies of ligand binding site topology. This basic information may be beneficial in the synthesis of more efficient drugs for the treatment of heart ailments.